Stem cell therapy caused nasal tumour on paraplegic's back

Nasal cells began to grow in the patient's spine nearly a decade after the stem cells were implantationShutterstock

A young paraplegic woman who
underwent spinal stem cell therapy developed a growth in her back
made up of nasal cells eight years later.

The team from the University of Iowa Hospitals and Clinics that
removed and investigated the growth has reported the anomaly in a
paper published in the Journal
of Neurosurgery: Spine. Although the case is a rare
occurrence (the first of its kind, that we know of) the authors
admit this may simply be because patients that undergo therapy are
not monitored long enough, and either way it provides ample
evidence attesting to our lack of understanding around programming
and controlling stem cell proliferation and differentiation
post-transplant.

Human trials for this type of therapy are still at the very
early stages, but animal trials have had some promising results.
Several different types of cells have been experimented with for
implantation including schwann cells (these surround nerves and
sometimes grow on the spinal cord post-injury), foetal neural cells
(with successes in rat studies) and nasal olfactory
ensheathing cells (these are extracted from the lining of the nose
and were the ones used in this particular case study).

The patient in question was just 18 years old when she suffered
an injury during a car accident. She had been paraplegic for three
years when she opted to undergo surgery, implanting olfactory
mucosal cells into the injury site. These cells originate in the
roof of the nasal cavity and have the ability to take on the
characteristics of other cells in the body because they are
partially made up of progenitor cells (adult stem cells). They also
contain olfactory ensheathing cells, often used in spinal cord
therapy trials. This is all despite, as the authors note, the fact
that: "the ability of these cell types to differentiate into
organised neural tissue in humans or support new neural growth in
humans in the setting of spinal cord injury is unclear."

The location of the transplantation was not divulged in the
Spine paper, but the New Scientist reports that it was carried out
as part of an early stage trial in the Hospital de Egas Moniz in
Lisbon, Portugal. In a paper, the Lisbon team revealed that out of
20 candidates, 11 regained some sensation and one person's
paralysis actually worsened.

The woman's therapy did not flag up any issues at the time of
implantation, but eight years down the line she complained of
worsening back pain that had already been ongoing for a year. Scans
at the University of Iowa Hospitals and Clinics revealed a mass,
thick like mucus and surrounded by fibrous walls, on the spinal
cord, at the site of the cell implantation. The investigators
explain that the mass was made up "mostly of cysts lined by
respiratory epithelium, submucosal glands with goblet cells, and
intervening nerve twigs". Nasal elements were growing.

The mass was pressing against the spinal cord, causing the
patient discomfort and threatening her spine. When it was
extracted, the team could confirm it came from the neural stem-like
cells implanted eight years earlier, because the cysts contained a
network of non-functioning nerves that were separate from the spine
(suggesting they were new) and bone.

"The presence of these nerves within the mass indicates the
capacity of olfactory mucosa to support nerve fibre regeneration or
new nerve formation," write the team.

In total, the mass was made up of two major parts, measuring 1.4
x 0.8 x 0.7 cm and 1.6 x 1.3 x 0.7 cm. When they were removed, the
patient's pain immediately subsided.

These kinds of trials have been ongoing for years, but the fears
have been that stem cells -- which have the ability to turn into
any cell in the body if programmed to -- could just as easily
mutate into something that is not intended, and create tumours in
the long term.

The authors, however, are not suggesting this case study should
cause alarm. Rather, they have used the article to make a call for
physicians to monitor patients that undergo such therapy for far
longer, since we have evidence that things can rapidly change.
According to the paper, human clinical trials into olfactory
mucosal cell transplantation usually have a follow-up time of just
four years at most.

The case study does also provide an opportunity to learn
something about how transplantation techniques could potentially
impact success.

The authors explain that in this particular trial, the olfactory
mucosa was transplanted directly to the site of damage. In other
trials, however, the cells were first treated and purified.

"There has been limited follow-up of these patients, and there
have been few publications following the initial feasibility and
safety trials," write the authors. "It is unclear if the difference
in isolation and preparation of olfactory stem cells results in
different outcomes." It's definitely worth investigating,
though.

Only two other growths from stem cell therapy have been reported
in scientific literature, say the authors. But these were very
specific cases, not at all similar to this instance of spinal cord
therapy. Apparently 140 people have undergone the same therapy at
the Lisbon hospital, but Jean Peduzzi-Nelson of Wayne State
University in Detroit told the New Scientist this problem has occurred, to date,
in less than 1 percent of those who have received olfactory mucosal
cells.

Still, it shows this important area is vastly under studied.

"These cases should not deter the advancement of stem cell
research and bench-to-bedside clinical trials," write the authors.
"However, they do stand as a warning to the scientific and medical
communities."